Antipsychotic Drug Overdose

KEY FEATURES

• Conventional antipsychotics act mainly on central nervous system dopamine receptors; examples include

  • Chlorpromazine

  • Haloperidol

  • Droperidol

• Newer "atypical" antipsychotics also interact with serotonin receptors; examples include

  • Risperidone

  • Olanzapine

  • Ziprasidone

  • Quetiapine

  • Aripiprazole

CLINICAL FINDINGS

• Conventional phenothiazines (particularly chlorpromazine) at therapeutic doses may induce drowsiness and mild orthostatic hypotension in as many as 50% of patients

• Large doses may cause

  • Obtundation

  • Miosis

  • Severe hypotension

  • Tachycardia

  • Convulsions

  • Coma

• Abnormal cardiac conduction may occur, resulting in prolongation of QRS or QT intervals (or both) and ventricular arrhythmia

• Quetiapine is more likely to cause coma and hypotension

• An acute extrapyramidal dystonic reaction may occur with therapeutic or toxic doses

  • Spasmodic contractions of the face and neck muscles, extensor rigidity of the back muscles, carpopedal spasm, and motor restlessness

  • More common with haloperidol and other butyrophenones, less common with atypical drugs

• Severe rigidity, hyperthermia, and metabolic acidosis (neuroleptic malignant syndrome) may occasionally occur and are life-threatening

• Atypical antipsychotics have also been associated with weight gain and diabetes mellitus, including diabetic ketoacidosis

DIAGNOSIS

• Largely based on history of exposure

• Most agents are not detected in routine rapid toxicology screens

• Serum levels are not helpful

• ECG monitoring for QRS, QT prolongation

TREATMENT

• Emergency and supportive measures

  • Activated charcoal for large or recent ingestions

  • For severe hypotension, treatment with intravenous fluids and vasopressor agents may be necessary

  • Treat hyperthermia as outlined

  • Maintain ECG monitoring

• Specific treatment

  • Hypotension often responds to intravenous saline boluses

  • Cardiac arrhythmias associated with widened QRS intervals on the ECG may respond to intravenous sodium bicarbonate as is given for tricyclic antidepressant overdoses

  • For prolongation of the QT interval and torsades de pointes

    • Intravenous magnesium

    • Consider overdrive pacing

  • For extrapyramidal signs

    • Diphenhydramine, 0.5–1 mg/kg intravenously, or

    • Benztropine mesylate, 0.01–0.02 mg/kg intramuscularly

    • Continue with oral doses for 24–48 hours

  • Bromocriptine (2.5–7.5 mg orally daily) may be effective for mild or moderate neuroleptic malignant syndrome.

  • Dantrolene (2–5 mg/kg intravenously) has also been used for muscle rigidity but is not a true antidote

  • For severe hyperthermia, perform rapid neuromuscular paralysis